Feasibility of visfatin as a molecular marker of breast cancer / 中国医师杂志

Objective:To investigate the value of visfatin in the differential diagnosis of benign and malignant breast tumors and the feasibility of visfatin as a molecular marker of breast cancer.Methods:A total of 195 breast cancer patients hospitalized in the Cancer Hospital of The University of Chinese Academy of Sciences from December 2017 to July 2018 were selected as the breast cancer group, all of them were women. 80 patients with benign breast diseases in the same period were randomly selected as the breast benign disease group, all of them were women. 80 female employees with normal physical examination in the same year were selected as the normal control group. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum level of visfatin. Logistic regression was used to analyze the relationship between visfatin and clinicopathological features of breast cancer. Receiver operating characteristic (ROC) curve was drawn to get area under curve (AUC) value, and the diagnostic efficacy was analyzed.Results:The serum visfatin level in breast cancer group was significantly higher than that in benign breast disease group and normal control group ( P<0.05). Univariate analysis showed that the serum visfatin level was related to lymph node metastasis, tumor node metastasis (TNM) stage and body mass index (BMI) (all P<0.05). The serum visfatin level was positively correlated with TNM stage and lymph node metastasis of breast cancer patients ( r=0.336, P=0.043; r=0.632, P=0.027, respectively). Multivariate regression analysis showed that lymph node metastasis was a risk factor for serum visfatin [ OR=1.098, 95% CI(1.073, 1.226), P=0.02]. According to the ROC curve of serum visfatin level in benign breast disease group and normal group, the AUC of serum visfatin were 0.652 and 0.701, respectively. When the Youden index was the highest, the sensitivity was 52.30% and 55.90% respectively, and the specificity was 73.10% and 75.0% respectively. Conclusions:Serum visfatin level can be used to distinguish benign and malignant breast cancer patients. It has a certain clinical value in the auxiliary diagnosis of breast cancer, and may be used as a potential molecular marker of breast cancer.

Clinicopathological features in predicting pCR of NAC for breast cancer based on Logistic regression and Nomogram / 中华内分泌外科杂志

Objective:To investigate the predictive value of the clinicopathological features of breast cancer for pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) and to establish a predictive model based on the clinicopathological features.Methods:Clinicopathological data collected from 182 patients who underwent NAC and surgical treatment in Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine from Jan. 2013 to Dec. 2019 were retrospectively analyzed. The univariate and multivariate analysis were used to analyze the relationship between clinicopathological features and pCR after neoadjuvant chemotherapy. The predictive value in predicting the efficacy of NAC was evaluated, the receiver operating characteristic (ROC) curve and Nomogram prediction model were constructed.Results:Multivariate Logistic regression analysis showed that progesterone receptor (PR) , human epidermal growth factor 2 (HER2) and platelet distribution width (PDW) were independent predictors of pCR after NAC for breast cancer. The area under the curve (AUC) of model for predicting efficacy of NAC was 0.810 (95% CI:0.745-0.864) and the sensitivity and specificity was 68.75% and 82.67% respectively when the Jordan Index is at its maximum. Conclusion:ER-, HER2+ and PDW≤13.4% show better efficacy of NAC. The Nomogram model based on them can accurately predict the efficacy of NAC and can provide a reference for the selection of treatment options in clinical diagnosis and treatment.

Plasma levels of D-dimer in patients with ovarian cancer and its relation to clinicopathologic characteristics of disease / 中国医师杂志

Objective:To investigate the plasma D-dimer levels in patients with ovarian cancer, and the relationship between plasma D-dimer and clinical pathologic characteristics of disease.Methods:A total of 268 patients with ovarian tumor who were diagnosed and treated by Zhejiang Cancer Hospital from January 2017 to August 2018 were retrospectively analyzed. Plasma D-dimer levels were measued by immunoturbidimetric assay in 176 ovarian cancer patients and 92 benign ovarian tumor patients. Univariate and multivariate logistic regression were used to analyze the relationship between plasma D-dimer and clinicopathological factors of ovarian cancer.Results:The plasma D-dimer level in patients with ovarian cancer was significantly higher than that in patients with benign ovarian tumor ( P<0.001); univariate analysis and multivariate logistic regression analysis showed that plasma D-dimer was closely related to International Federation of Gynecology and Obstetrics (FIGO) stage of ovarian cancer patients ( P<0.001); the plasma D-dimer level of ovarian cancer patients after treatment was significantly decreased ( P<0.001). Conclusions:Patients with ovarian cancer has coagulation disorders before treatment. The level of plasma D-dimer reflects the malignant degree of ovarian cancer and is closely related to the stage and progress of ovarian cancer. The level of D-dimer has important value in serological diagnosis and clinical application of ovarian cancer.

Discussion on the necessity of Delphian lymph node dissection for papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To investigate the clinical significance of Delphian lymph node (DLN) dissection in papillary thyroid cancer (PTC) .Methods:The correlation of DLN detection and metastasis in 208 PTC patients with various clinical and pathological features was analyzed retrospectively. The value of DLN metastasis in predicting PTC high-risk features was evaluated, and the tendency of surgical selection for PTC with DLN metastasis was also discussed.Results:① Of 208 PTC patients, DLN was detected in 144 patients (69.23%) . The detection rate of DLN was related to gender, number of central lymph nodes (excluding DLN) removed and metastasis (all P<0.05) . Male, greater number of nodes in the central compartment (excluding DLN) was more favorable for DLN detection. ② The rate of DLN metastasis was 18.27% (38/208) . In the univariate analysis, DLN metastasis was significantly associated with the following variables:gender, whether it is microcarcinoma, isthmus involvement, number of lesions, extrathyroidal extension, tumor size, number of central lymph nodes (excluding DLN) removed and metastasis (all P<0.05) . In the multivariate analysis, tumor size larger than 1 cm, isthmus involvement and greater number of central lymph nodes (excluding DLN) metastasis were independent risk factors of DLN metastasis ( P<0.05) . ③ The sensitivity of DLN metastasis to predict extranodal invasion, central and lateral lymph node metastasis was 54.54%, 37.36% and 62.86%, with specificity of 78.69%, 92.45% and 55.56%, respectively. ④ Patients with DLN metastasis were more likely to receive total thyroidectomy, bilateral central lymph node dissection, and lateral cervical lymph node dissection. Conclusions:Due to high rate of DLN detected and metastasis, DLN should be routinely dissected. Patients with DLN metastasis predict high risk characteristics of PTC and extensive lymph node metastasis, which is of clinical significance for lymph node dissection.

Clinical significance of serum carcinoembryonic antigen in predicting lymph node metastasis for resectable medullary thyroid carcinoma / 中华内分泌外科杂志

Objective:To investigate the clinical application value of serum carcinoembryonic antigen (CEA) level in predicting lymph node metastasis of resectable medullary thyroid carcinoma (MTC) .Methods:140 patients of resectable MTC from Zhejiang Cancer Hospital and Hangzhou First People’s Hospital from Jan. 2009 to Feb. 2019 were included. The relationship of serum CEA and lymphatic metastasis was retrospectively analyzed in 140 patients of resectable MTC, and the clinical significance of serum CEA for predicting total lymph node, central lymph node, lateral lymph node and upper mediastinal lymph node metastasis was also evaluated.Results:The positive rate of serum CEA in resectable MTC was 77.14%. The expression level of serum CEA in resectable MTC with lymph node metastasis was significantly higher than those without lymph node metastasis ( P<0.001) . Spearman correlation analysis further indicated that the level of serum CEA expression was positively correlated with the number of lymph node metastases of resectable MTC patients ( P<0.001) . The area under curve of predicting lymphatic metastasis of total lymph node, central lymph node, lateral lymph node and upper mediastinum was 0.773, 0.768, 0.827 and 0.847. When the cut-off value of serum CEA was 6.58, 11.43, 15.74 and 30.45 ng/ml, respectively, the sensitivity of serum CEA to predict total, central, lateral neck and upper mediastinal lymph node metastasis was 88.46%, 81.43%, 85.00%, 95.00%, and the specificity was 56.45%, 60.00%, 71.25%, and 69.17%, respectively. Conclusion:Serum CEA has a high positive expression rate in resectable MTC, and its expression level has important clinical significance in evaluation of lymphatic metastasis.

Establishment of methylation detection method for Septin 9 gene and its application in plasma specimen detection in colorectal cancer / 国际检验医学杂志

Objective To establish the blood Septin9 methylation detection system for early screening of colorectal cancer based on fluorescence PCR technology .Methods The PCR primer of Septin9 was designed by searching the CpG island site of Septin9 methylation in the NCBI database .The high methylation site of Septin9 gene promoter region was confirmed by PCR amplification and sequencing after extracting DNA from colorectal cancer and para-carcinoma tissues .The fluorescence PCR and TaqMan probe detection technique was designed by aiming at high methylation site for constructing the plasma sample methylation detection sys-tem .Then its accuracy ,specificity ,repeatability and minimum detectable amount were performed the assess-ment and analysis .The SETP9 methylation detection was performed in plasma samples from 57 cases of color-ectal cancer and 30 healthy persons .Results The high methylation site of Septin9 gene in tissue samples was confirmed by sequencing .This site served as the target for designing fluorescence PCR detection system .After assessment ,the accuracy ,specificity and repeatability of this detection system were 100％ ,the lowest detection amount reached 0 .1 ng/μL .Among the plasma samples in 57 cases of colorectal cancer ,the positive rate of Septin9 methylation site detection was 71 .92％ (41/57) and the positive rate of in the patients with pathologi-cal stage Ⅰ and Ⅱ of colorectal cancer reached 64 .2％ .But Septin9 gene had no methylation in plasma of healthy population .Conclusion The plasma fluorescence PCR detection system with Septin9 gene methylation as the target has the characteristics of high sensitivity ,high specificity and high accuracy ,which is the reliable detection technique for the early screening of colorectal cancer and has good clinical application prospect .

Clinical significance of detection for mutated BRAF gene in thyroid nodules based on amplification refractory mutation system / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the feasibility of detection for mutated BRAF V600E gene based on amplification refractory mutation system(ARMS),and to evaluate its clinical significance of BRAF V600E gene mutation in thyroid nodules.METHODS The method of ARMS was used to detect BRAF V600E mutation status in 179 patients with PTC and 115 patients with benign lesions.The diagnosis index of BRAF V600E mutation status for identifying the nature of the thyroid nodule was calculated.The potential correlation between BRAF V600E mutation and PTC clinicpathological characteristics was also analyzed.RESULTS Detection of BRAF V600E mutation status in thyroid lesions based on ARMS was feasible and believable.The positive rate of mutated BRAF V600E gene in PTC was 82.68％,whereas the rate in benign lesions was only 1.74％,indicating statistical differences between the two groups(x2=183.568,P＜0.01).The diagnostic sensitivity of BRAF V600E mutation was 82.68％,specificity was 98.26％,accuracy was 88.76％,and Youden index was 0.8094.There was no associations between the BRAF V600E mutation status and PTC clinicpathological characteristics(eg.gender,age,tumor size,numbers of lesions,bilateral lesions,extrathyroidal extension and lymph node metastasis).CONCLUSION Detection of BRAF V600E mutation based on ARMS has higher sensitivity and specificity in distinguishing PTC from benign lesions,indicating BRAF V600E gene is an ideal marker of PTC for clinical early diagnosis.

Clinical significance of serum microRNA-222-3p expression in papillary thyroid carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the expression of serum miR-222-3p in papillary thyroid carcinoma and its clinical significance.METHODS Total RNA in serum was extracted from 121 patients of papillary thyroid carcinoma and benign thyroid diseases.The reverse transcription quantitative real-time polymerase chain reaction(qRT-PCR) method was used to detect the expression of miR-222-3p,and then the potential correlation between serum miR-222-3p and clinical pathological characteristics of papillary thyroid carcinoma was analyzed.The receiver operating characteristic area under the curve(ROCAUC) and their index for diagnosis evaluation were also calculated.RESULTS The median expression level of serum miR-222-3p in papillary thyroid carcinoma patients was significantly higher than that of control group (2.2188 vs 0.7022,P=0.002).Although the expressions of serum miR-222-3p was not associated with the gender,age,capsule invasion,TNM stage,but it was positively correlated with tumor size,bilateral involvement,lesion quantity and lymph node status.ROC curve analysis showed that the specificity and sensitivity of the miR-222-3p diagnosis of papillary thyroid cancer were 79.75％ and 61.90％,respectively,while the ROC-AUC was 0.717.CONCLUSION The serum miR-222-3p is over expressed in papillary thyroid carcinoma and its expression is significantly correlated with tumor progression.It will be helpful for PTC diagnosis.

Progress study of miRNA in papillary thyroid carcinoma / 中华内分泌外科杂志

MiRNAs represent a class of short endogenous non-coding RNAs regulating gene expression at mRNA post-transcriptional level in many biological processes,including differentiation,proliferation,development and apoptosis.The deregulation of miRNA expression is believed to be an important regulator of tumor development.Increasing evidence has revealed the abnormal expression of miRNA in papillary thyroid carcinoma,indicating the important role in PTC invasion mechanism,clinical diagnostic value,efficacy evaluation,recurrence monitoring and prognosis judgement.

Clinical diagnostic value of serum amyloid A in patients with lung cancer / 中华检验医学杂志

Objective To evaluate the clinical value of SAA by detecting their expression levels in patients with lung cancer and the analysis of the relativity of SAA for early diagnosis.Methods There are 243 cases specimens obtained from lung cancer patients who were newly diagnosed and without any treatment in Zhejiang Cancer Hospital from April 2014 to June 2015.The 243 lung cancer individuals were 147 male, and 96 female, their ages ranged from 29 to 85 years, with an average age of 63 years.The distribution of pathological type was as follows:95 patients were adenocarcinoma, 102 patients were squamous carcinoma, and 46 patients were small cell carcinoma.The distribution of TNM staging systems was as follows: 59 patients in stage 1and stage 2, 54 patients in stage 3, and 130 patients in stage 4.While 179 cases physical examination as the control.There were 94 individuals male, and 85 individuals female.Their ages ranged from 26 to 86 years, with an average age of 61 years.By using latex enhanced immune turbidimetric method, serum SAA concentrations in patients with lung cancer and healthy controls were checked on the Hitachi-7600 automated chemistry analyzer ( Hitachi ).The comparisons of all analyses values between healthy controls and lung cancer were estimated by two independent samples nonparametric tests ( Mann-Whitney U).The association between SAA and lung cancer prognostic factors such as age, smoking status and metastasis, was evaluated by spearman correlation and multivariate analysis.Results The median and interquartile spacing of SAA concentration was 42.36 mg/L (9.35, 74.22) in lung cancer patients.While 24 mg/L ( 3.25, 21.45 ).The median level of SAA in lung cancer patients (42.36 mg/L) were significantly higher than in healthy controls (11.24 mg/L), and difference reached statistically significant (Z=-2.403,P=0.006).Nevertheless, there was no significant difference in SAA concentrations among the different pathological types(Z=-1.013, P=0.339), ages (Z=0.578, P=0.458) and gender(Z=0.726, P=0.246) of lung cancer patients.While the level of SAA in has smoking status (Z=-2.282, P=0.013) and distant metastasis (Z=-2.138, P=0.017) of lung cancer was higher.By drawing ROC curve, the cut off value of SAA in distinguishing lung cancer with healthy control was 14.48 mg/L.Meanwhile, the AUC was 0.811, the accuracy is 89.12% and the sensitivity was 88.73%.Serum concentration was positively related with smoking status ( r =0.331, P =0.018 ) and distant metastasis ( r =0.372, P=0.015 ) by Spearman correlation analysis .Conclusion Serum SAA concentrations may contribute to the auxiliary diagnosis of lung cancer, evaluate the clinical stage and distant metastases of lung cancer.

Application value of combined detection of serum human epididymis protein 4, cancer antigen 125 and cancer antigen 19-9 in early endometrial carcinoma / 中国医师进修杂志

Objective To investigate the application value of combined detection of serum human epididymis protein 4 (HE4),cancer antigen 125 (CA125) and cancer antigen 19-9 (CA 19-9) in early endometrial carcinoma.Methods Two hundred and six patients with early endometrial carcinoma (endometrial carcinoma group) and 118 patients with uterine fibroids (uterine fibroids group) were selected.Serum level of HE4 was measured by enzyme linked immunosorbent assay (ELISA),and serum levels of CA 125 and CA 19-9 were measured by chemiluminescence immunoassay(CLIA).The positive rates of serum HE4,CA125 and CA19-9 in the 2 groups were compared.The changes between pre-and post-operative in the serum levels of serum HE4,CA125 and CA19-9 were compared in 147 endometrial carcinoma patients.Results The serum levels of HE4 and CA19-9 in endometrial carcinoma group were significantly higher than those in uterine fibroids group [76.57 (56.92-104.60) pmol/L vs.56.75 (48.33-68.91) pmol/L,13.26(6.07-25.90) kU/L vs.7.64(3.76-16.45) kU/L],there were statistical differences (P =0.000),there was no statistical difference in serum level of CA125 between the 2 groups (P=0.106).In endometrial carcinoma group,the positive rates of serum HE4 and HE4 + CA125 + CA19-9 were significantly higher than the positive rates of serum CA125,CA19-9,CA125+CA19-9,there were statistical differences (P ＜ 0.01).The positive rates of serum HE4,CA19-9,HE4 +CA125,HE4 +CA19-9 and HE4 +CA125 +CA19-9 in endometrial carcinoma group were significantly higher than those in uterine fibroids group,there were statistical differences (P ＜ 0.01).The serum levels of HE4,CA125 and CA19-9 in post-operative in 147 endometrial carcinoma patients were significantly lower than those in pre-operative,there were statistical differences (P ＜ 0.01).Conclusion The diagnostic value of serum HE4 in early endometrial carcinoma is better than CA125 and CA19-9,while combined detection of serum HE4,CA125 and CA19-9 can raise the positive rate and be helpful for therapeutic effect evaluation.

Clinical significance of preoperative measurement of serum human epididymis protein 4, CA125 and CA19-9 in endometrial cancer patients / 中华全科医师杂志

Preoperative serum specimens were collected from 249 endometrial cancers and 99 uterine leiomyomas and their concentrations of human epididymis protein 4 (HE4),CA 125 and CA 19-9 were detected.The indices of diagnostic evaluation were calculated.Preoperative serum concentrations of HE4,CA125 and CA19-9 in endometrial carcinoma group were significantly higher than those of control group.The areas under curve of HE4,CA125 and CA19-9 were 0.736,0.615 and 0.661 respectively and that of combiued markers was 0.774.At a 90％ specificity,the sensitivities for HE4,CA125,CA19-9 were 55.0％,26.9％ and 30.1％ while that of combined markers was 56.2％.HE4 is an ideal tumor marker for endometrial cancer and combined detection improves diagnostic rate.